There are two proteins that are deficient in von Willebrand's disease: von Willebrand factor and von Willebrand Antigen II. Each is present in platelet alpha granules (released by platelet activation) and colocalized in specific granules in cultured endothelial cells. Although no immunologic relationship between these two proteins can be demonstrated in plasma, serum, or platelets, recent studies demonstrate the synthesis of a complex for vWf and vW AgII within the endothelial cell that is cleaved upon secretion into the culture media. Studies will be performed to determine the structure and function of both vWf and vW AgII in plasma, platelets, and endothelial cells. Since vWf is cleaved by platelet calpain, studies will be performed to determine the significance of this fragmentation on the physiologic function of vWf and to determine ways in which vWF proteolysis can be avoided. Platelet vWf and vW AgII will be purified and their binding to platelet membrane receptors will studied in comparison to their plasma-derived counterparts. The synthesis of the vWf/vW AgII complex in endothelial cells will be studied to determine whether the complex is a precursor or a synthetic intermediate. Genetic studies will be performed with mRNA and cDNA probes. Endothelial cell proteins released by activation will be characterized and their use as specific indicators of endothelial cell activation will be determined.